Natural killer (NK) cells are a third subtype of lymphocytes besides B and T cells. NK cells provide an important immune function in the defense against viruses and other intracellular pathogens. Unlike B and T cells, NK cells do not exhibit specificity for antigen. They acquired their name because they can kill cells without prior stimulation by antigen. The killing of normal healthy cells is prevented by inhibitory receptors on NK cells that recognize major histocompatibility class I molecules. A large number of receptors, both activating and inhibitory, that regulate the cytotoxic response of NK cells have been described. In order to evaluate the contribution of individual receptors to the control of NK cell activation, mice defective in a given NK cell inhibitory receptor have been used. In addition, a search for the mouse receptor equivalent to the killer cell immunoglobulin-like receptors (KIR) on human NK cells was undertaken. The mouse inhibitory receptor gp49B is interesting because it is expressed on several cell types that can release granules during activation. Such cells include NK cells, mast cells, and neutrophils. Using mice deficient in gp49B and in vivo models of allergic responses, we observed enhanced degranulation by mast cells, and enhanced infiltration of neutrophils and eosinophils in lungs and at the site of challenge with allergen. We established that gp49B is expressed by eosinophils, thus expanding the number of degranulating cell types that are under negative control by gp49B. Severe pathology due to massive eosinophil infiltration of lungs during allergic responses in mice deficient in gp49B provided clears evidence for an essential role for this inhibitory receptor in controlling eosinophil responses. A property common to the immune system and the nervous system is regulation by a highly complex and adaptable network of cellular interactions. Major histocompatibility complex (MHC) class I molecules, which are ligands of antigen-specific receptors on CD8 T cells and of inhibitory receptors on NK cells, have an important and surprising role in the control of activity-dependent neuronal plasticity in the central nervous system (CNS). While expression of MHC class I molecules in neurons has been reported, corresponding immune receptors have not been identified in the central nervous system. Here we show selective expression of a killer cell imunoglobulin-like receptor (KIR) gene in subregions of the mouse brain where synaptic plasticity and neurogenesis occur, including olfactory bulbs, rostral migratory stream, and dentate gyrus of hippocampus. These results suggest new functions for KIR in the CNS.